Seniors Will Cheer Researchers Who
Have Proven How Memory Can Be Turned On and Off
NIH funded study is first to prove
connections between neurons controls memory
2014 – There is news out of the National Institutes of Health that
should make seniors very happy or at least hopeful. The tantalizing
image is of a switch that can turn memory or off. What these scientists
have done is turn memory off and then back on using a flash of light in
genetically engineered rats. It is the first clear cause-and-effect
evidence that the connections between neurons in our brains are what
make memory work.
“Our results add to mounting
evidence that the brain represents a memory by forming assemblies of
neurons with strengthened connections, or synapses, explained
Roberto Malinow, M.D., Ph.D., of
the University of California, San Diego (UCSD), a grantee of the NIH’s
National Institute of Mental Health (NIMH).
“Further, the findings suggest that
weakening synapses likely disassembles neuronal assemblies to inactivate
Roger Tsien, Ph.D., a grantee of
NIH’s National Institute on Neurological Disorders and Stroke (NINDS),
and other UCSD colleagues, report June 1, 2014 in the journal Nature on
their findings using cutting edge optical/gene-based technology.
“Beyond potential applications in
disorders of memory deficiency, such as dementia, this improved
understanding of how memory works may hold clues to taking control of
runaway emotional memories in mental illnesses, such as post-traumatic
stress disorder,” said NIMH director Thomas R. Insel, M.D.
Neuroscientists have long suspected
that strengthened connections between neurons – called long-term
potentiation (LTP) – underlies memory formation, But proof had remained
elusive, until this study funded by NIH.
The Malinow team proved it by
detecting LTP when forming a memory, removing the memory with a process
known to reverse LTP, and then bringing the memory back via LTP – all by
modifying the strength of synapses in a memory circuit.
To gain the precise control needed
to show such a cause-and-effect relationship, Malinow’s team turned to
one of neuroscience’s most powerful new tools:
optogenetics. It adapts the same
cellular machinery that allows primitive organisms like algae to be
controlled by light from the sun to control specific brain circuit
components instantly with a laser – even in a behaving animal.
In conventional rodent fear
conditioning experiments, a tone is paired with a foot shock to induce a
fear memory of the tone. If the memory is active, the animal freezes and
shows reduced reward-seeking behaviors when it hears the tone. Instead
of the tone, Malinow’s team paired the shock with direct optogenetic
stimulation, lighting up a specific group of neurons in a known auditory
fear memory circuit.
Such precise targeting wasn’t
possible with earlier electrical stimulation techniques. “It’s just a
jungle in the brain – too many nerve cells coming through in any one
place,” explained Malinow.
By varying the pattern of
optogenetic stimulation, the researchers were able to strengthen
connections between neurons in the circuit by promoting LTP or weaken
the connections by promoting a countervailing process called long-term
depression (LTD). This made it possible to readily form a fear memory,
remove it, and then bring it back.
Moreover, upon closer optogenetic
probing in postmortem brains, the targeted circuit neurons showed
telltale changes in sensitivity of brain chemical messenger systems.
These changes confirmed the hypothesized role of strengthening and
weakening of synaptic connections in the switching on-and-off of the
“We have shown that the damaging
products that build up in the brains of Alzheimer’s disease patients can
weaken synapses in the same way that we weakened synapses to remove a
memory,” said Malinow. “So this line of research could suggest ways to
intervene in the process.”
“In addition to eliminating any
doubt about a link between LTP/LTD with memories, this work highlights
the staggering potential of precision targeting and circuit manipulation
for alleviating maladaptive memories,” said project officer Chiiko
Asanuma,Ph.D., of the NIMH Division of Neuroscience and Basic Behavioral
"This work provides a nice
demonstration of how the field of neuroscience is being transformed by
the types of technologies that are at the heart of President Obama's
BRAIN Initiative,” said Edmund
Talley, Ph.D., program director at the NINDS.
Engineering a memory with LTD and
LTP. Nabavi S, Fox R, Proulx CD, Lin JY, Tsien RY, Malinow R. Nature,
advanced online publication, June 1, 2014.
About the National Institute of
Mental Health (NIMH): The mission of the NIMH is
to transform the understanding and treatment of mental illnesses through
basic and clinical research, paving the way for prevention, recovery and
cure. For more information, visit
the nation’s leading funder of research on the brain and nervous system.
The mission of NINDS is to seek fundamental knowledge about the brain
and nervous system and to use that knowledge to reduce the burden of
About the National Institutes
of Health (NIH): NIH, the nation's
medical research agency, includes 27 Institutes and Centers and is a
component of the U.S. Department of Health and Human Services. NIH is
the primary federal agency conducting and supporting basic, clinical,
and translational medical research, and is investigating the causes,
treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit
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